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蜂毒素与化疗药物的协同作用及其可能机制的实验研究 被引量:5

Synergistic Interaction between Melittin and Chemotherapeutic Agents and Their Possible Mechanisms:an Experimental Research
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摘要 目的分别观察蜂毒素联合5-氟尿嘧啶(5.Fu)、顺铂(DDP)、多西紫杉醇(TXT)抗人胃癌细胞株BGC-823增殖的效果,并初步探讨其作用机制。方法运用中效原理进行统计分析,绘制5-Fu、DDP和TXT单药及分别与蜂毒素联合用药对该肿瘤细胞生长的剂量一效应曲线,确定联合用药时对肿瘤细胞的效应(FA)与合用指数(CI)的关系,判定药物间的相互作用。运用实时荧光定量PCR法检测蜂毒素分别联合5.Fu、DDP和TXT作用人胃癌细胞株BGC.823后对化疗药物相关基因表达的改变。结果(1)在一定的浓度范围内蜂毒素单药与3种化疗药物单药均对BGC-823细胞显示出了明显的生长抑制效果。(2)蜂毒素联合5-Fu作用于BGC-823细胞时,FA在0.35~0.75时,CI〈1。蜂毒素联合DDP作用于BGC-823细胞时,FA在O.55左右,CI=1;FA〈0.55,CI〈1。蜂毒素联合TXT作用于BGC-823细胞时,整个区间内均可见CI〈1。(3)蜂毒素分别与3种化疗药物联合作用于细胞后,化疗药物相关基因胸苷酸合成酶(thymidylatesynthetase,TS)、切除修复交叉互补基因1(excisionrepaircross—complementinggene1,ERCCl)、乳腺癌易感基因1(breastcancersusceptibilitygene1,BRCAl)、β微管蛋白Ⅲ(β—tubu-nⅢ,TUBB3)和微管相关蛋白tau(rrlicrotubule—associatedproteintau,MAPT)的表达明显低于空白对照组(P〈0.01)。结论蜂毒素具有增强5.Fu、DDP、T)(T对胃癌细胞BGC-823生长抑制效果的协同作用,其作用机制可能与下调化疗相关基因的表达有关。 Objective To evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms. Methods Median effect anal- ysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the rela- tionship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC4323 cells with or without treatment were measured by real-time fluorescent quantitative PCR. Results (1) Both melittin and chemotherapeu- tic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu + melittin, when FA ranged between 0.35 -0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI =1 ; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT +melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), β-tubulin Ⅲ (TUBB3), and microtubule-associated protein tau (MAPT). Conclusions Melittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might beassociated with down-regulating chemotherapeutic agent-associated genes.
出处 《中国中西医结合杂志》 CAS CSCD 北大核心 2014年第2期224-229,共6页 Chinese Journal of Integrated Traditional and Western Medicine
基金 江苏省六大高峰人才项目(No.WS037) 江苏省中医药管理局领军人才项目(No.LJ200908) 江苏高校优势学科建设工程资助项目(PAPD)
关键词 蜂毒素 人胃癌细胞株BGC-823 协同作用 实时荧光定量PCR 化疗药物相关基因 melittin human gastric cell line BGC-823 synergistic effect Real time PCR chemo-therapeutic agent-associated gene
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